The “dual problem” of U.S. population health is that population health is poor, while health care spending is high. These issues are interrelated, but only partly so. Poor population health does increase the need for health care services, which tends to increase spending. But the more important roots of poor population health lie in social policy rather than in health care—particularly an inadequate social insurance system that leads to many people being denied the income needed for health. Further, high spending is chiefly related to high prices, not high volumes, for health care services. This stems from a private, administratively wasteful, multipayer approach to health care finance in which no entity has sufficient monopsony power to hold down prices. This article discusses several ways to address these issues, with diabetes as an exemplary case. Two central themes are 1) the need for a better system of income supports to help ensure the conditions that promote health and 2) the need to reform our approach to health care finance, so as to address wasteful spending and help orient health care toward providing consistent care across the life course. Ultimately, what’s keeping the U.S. from better population health is us. But we could fix that.
{"title":"What’s Keeping the U.S. From Better Population Health?","authors":"Seth A. Berkowitz","doi":"10.2337/dci25-0003","DOIUrl":"https://doi.org/10.2337/dci25-0003","url":null,"abstract":"The “dual problem” of U.S. population health is that population health is poor, while health care spending is high. These issues are interrelated, but only partly so. Poor population health does increase the need for health care services, which tends to increase spending. But the more important roots of poor population health lie in social policy rather than in health care—particularly an inadequate social insurance system that leads to many people being denied the income needed for health. Further, high spending is chiefly related to high prices, not high volumes, for health care services. This stems from a private, administratively wasteful, multipayer approach to health care finance in which no entity has sufficient monopsony power to hold down prices. This article discusses several ways to address these issues, with diabetes as an exemplary case. Two central themes are 1) the need for a better system of income supports to help ensure the conditions that promote health and 2) the need to reform our approach to health care finance, so as to address wasteful spending and help orient health care toward providing consistent care across the life course. Ultimately, what’s keeping the U.S. from better population health is us. But we could fix that.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"164 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer R. Snaith, Ruth Frampton, Dorit Samocha-Bonet, Jerry R. Greenfield
OBJECTIVE Overweight and obesity are prevalent in type 1 diabetes and contribute to cardiovascular risk. Tirzepatide, a gastric inhibitory polypeptide and glucagon-like peptide 1 receptor coagonist, has not been studied in type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted a 12-week, phase 2, double-blind, placebo-controlled trial in adults with type 1 diabetes and BMI >30 kg/m2. Participants were randomized to once-weekly subcutaneous tirzepatide (2.5 mg for 4 weeks, 5.0 mg for 8 weeks) or placebo. The primary end point was change in body weight at 12 weeks. RESULTS Twenty-two of 24 adults with type 1 diabetes completed the study. After 12 weeks, the mean change in weight was −10.3 kg (95% CI −12.8 to −7.7 kg) in the tirzepatide group and −0.7 kg (95% CI −1.4 to 2.8 kg) in the placebo group, with an estimated treatment difference of −8.7 kg (95% CI −12.0 to −5.5 kg; P < 0.0001), representing 8.8% weight loss. In the tirzepatide group, 100% and 45% of participants experienced weight loss of ≥5% and ≥10% respectively, compared with 9% and 0% in the placebo group. Tirzepatide improved HbA1c (mean difference −0.4% [95% CI −0.7 to 0.0%] vs. placebo; P = 0.05) and reduced total daily insulin dose (−24.2 units/day tirzepatide and −0.3 units/day placebo; difference from baseline vs. placebo −35.1% [95% CI −46.5 to −21.3%; P = 0.0002]). There were no significant adverse events in either group. CONCLUSIONS Among adults with type 1 diabetes and obesity, tirzepatide was superior to placebo for weight loss over 12 weeks.
目的超重和肥胖在1型糖尿病患者中普遍存在，并会增加心血管风险。替西肽是一种胃抑制多肽和胰高血糖素样肽1受体促凝剂，尚未在1型糖尿病中进行研究。研究设计和方法我们在1型糖尿病和BMI的成人患者中进行了一项为期12周的2期双盲安慰剂对照试验。30 kg / m2。参与者随机接受每周一次的替西帕肽（2.5 mg， 4周，5.0 mg， 8周）或安慰剂治疗。主要终点是12周时体重的变化。结果：24名成人1型糖尿病患者中有22人完成了研究。12周后，替西肽组的平均体重变化为- 10.3 kg (95% CI为- 12.8至- 7.7 kg)，安慰剂组的平均体重变化为- 0.7 kg (95% CI为- 1.4至2.8 kg)，估计治疗差异为- 8.7 kg (95% CI为- 12.0至- 5.5 kg; P < 0.0001)，体重减轻8.8%。在替西帕肽组中，100%和45%的参与者分别经历了≥5%和≥10%的体重减轻，而安慰剂组为9%和0%。替西帕肽改善了HbA1c（与安慰剂相比平均差值为- 0.4% [95% CI - 0.7至0.0%],P = 0.05），并降低了每日总胰岛素剂量（替西帕肽为- 24.2单位/天，安慰剂为- 0.3单位/天，与基线相比差值为- 35.1% [95% CI - 46.5至- 21.3%,P = 0.0002]）。两组均无明显不良事件发生。结论：在患有1型糖尿病和肥胖症的成年人中，替西帕肽在12周的减肥效果优于安慰剂。
{"title":"Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial","authors":"Jennifer R. Snaith, Ruth Frampton, Dorit Samocha-Bonet, Jerry R. Greenfield","doi":"10.2337/dc25-2379","DOIUrl":"https://doi.org/10.2337/dc25-2379","url":null,"abstract":"OBJECTIVE Overweight and obesity are prevalent in type 1 diabetes and contribute to cardiovascular risk. Tirzepatide, a gastric inhibitory polypeptide and glucagon-like peptide 1 receptor coagonist, has not been studied in type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted a 12-week, phase 2, double-blind, placebo-controlled trial in adults with type 1 diabetes and BMI &gt;30 kg/m2. Participants were randomized to once-weekly subcutaneous tirzepatide (2.5 mg for 4 weeks, 5.0 mg for 8 weeks) or placebo. The primary end point was change in body weight at 12 weeks. RESULTS Twenty-two of 24 adults with type 1 diabetes completed the study. After 12 weeks, the mean change in weight was −10.3 kg (95% CI −12.8 to −7.7 kg) in the tirzepatide group and −0.7 kg (95% CI −1.4 to 2.8 kg) in the placebo group, with an estimated treatment difference of −8.7 kg (95% CI −12.0 to −5.5 kg; P &lt; 0.0001), representing 8.8% weight loss. In the tirzepatide group, 100% and 45% of participants experienced weight loss of ≥5% and ≥10% respectively, compared with 9% and 0% in the placebo group. Tirzepatide improved HbA1c (mean difference −0.4% [95% CI −0.7 to 0.0%] vs. placebo; P = 0.05) and reduced total daily insulin dose (−24.2 units/day tirzepatide and −0.3 units/day placebo; difference from baseline vs. placebo −35.1% [95% CI −46.5 to −21.3%; P = 0.0002]). There were no significant adverse events in either group. CONCLUSIONS Among adults with type 1 diabetes and obesity, tirzepatide was superior to placebo for weight loss over 12 weeks.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"1 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashni Goshrani, Rose Lin, Leonid Churilov, Michele Gaca, Christine Somerville, Andrew Farmer, Kamlesh Khunti, Elizabeth Holmes-Truscott, Negar Naderpoor, David O’Neal, Rury R. Holman, Elif I. Ekinci
BACKGROUND Adaptive and master protocol clinical trials offer significant advantages for diabetes research, including enhanced efficiency and personalized treatment strategies. PURPOSE This scoping review aimed to systematically map the use of adaptive and master protocol designs in interventional trials for type 1 and type 2 diabetes, identify research gaps, and highlight opportunities for broader implementation. DATA SOURCES A systematic literature search was performed using MEDLINE, Embase, CENTRAL, Emcare, Global Health, Web of Science, and clinical trial registries. Gray literature searches complemented database findings. STUDY SELECTION Studies using adaptive, platform, basket, or umbrella trial designs in people with type 1 or type 2 diabetes were included. DATA EXTRACTION Data were charted using a standardized form. Extracted variables included diabetes type, trial design, adaptive features, interventions, end points, and key findings. DATA SYNTHESIS Of 396 articles screened, 6 published adaptive trials met the inclusion criteria: 3 in type 1 diabetes, 1 in type 2 diabetes, and 2 in diabetes-related neuropathy. Most used adaptive features for dose finding, response-adaptive randomization, and sample size reestimation. No published platform, basket, or umbrella trials were identified. Six ongoing adaptive trials in type 1 diabetes were identified through registry searches, four under an adaptive platform master protocol. LIMITATIONS Despite a comprehensive search, some gray literature and unpublished studies may have been missed. Risk of bias was not assessed, consistent with scoping review methodology. CONCLUSIONS Adaptive and master protocol trials remain rare in diabetes. Overcoming barriers through targeted training and awareness, robust regulatory frameworks, and strategic incentives could support broader adoption.
适应性临床试验和主方案临床试验为糖尿病研究提供了显著的优势，包括提高效率和个性化治疗策略。目的：本综述旨在系统地描绘1型和2型糖尿病介入试验中适应性和主方案设计的使用情况，确定研究空白，并强调更广泛实施的机会。使用MEDLINE、Embase、CENTRAL、Emcare、Global Health、Web of Science和临床试验登记处进行系统的文献检索。灰色文献检索补充了数据库的发现。研究选择纳入了在1型或2型糖尿病患者中采用适应性、平台、篮子或伞式试验设计的研究。数据提取采用标准化表格绘制图表。提取的变量包括糖尿病类型、试验设计、适应性特征、干预措施、终点和关键发现。在筛选的396篇文章中，6篇已发表的适应性试验符合纳入标准：3篇1型糖尿病，1篇2型糖尿病，2篇糖尿病相关神经病变。大多数使用自适应特征进行剂量发现、反应自适应随机化和样本量重估。未发现已发表的平台、篮子或伞式试验。通过注册表检索确定了6项正在进行的1型糖尿病适应性试验，其中4项在适应性平台主方案下进行。尽管进行了全面的搜索，一些灰色文献和未发表的研究可能被遗漏。未评估偏倚风险，与范围评价方法一致。结论：适应性试验和主方案试验在糖尿病中仍然很少见。通过有针对性的培训和意识、健全的监管框架和战略激励措施来克服障碍，可以支持更广泛的采用。
{"title":"The Role of Adaptive and Innovative Trial Designs in Diabetes Research: A Scoping Review","authors":"Ashni Goshrani, Rose Lin, Leonid Churilov, Michele Gaca, Christine Somerville, Andrew Farmer, Kamlesh Khunti, Elizabeth Holmes-Truscott, Negar Naderpoor, David O’Neal, Rury R. Holman, Elif I. Ekinci","doi":"10.2337/dc25-1508","DOIUrl":"https://doi.org/10.2337/dc25-1508","url":null,"abstract":"BACKGROUND Adaptive and master protocol clinical trials offer significant advantages for diabetes research, including enhanced efficiency and personalized treatment strategies. PURPOSE This scoping review aimed to systematically map the use of adaptive and master protocol designs in interventional trials for type 1 and type 2 diabetes, identify research gaps, and highlight opportunities for broader implementation. DATA SOURCES A systematic literature search was performed using MEDLINE, Embase, CENTRAL, Emcare, Global Health, Web of Science, and clinical trial registries. Gray literature searches complemented database findings. STUDY SELECTION Studies using adaptive, platform, basket, or umbrella trial designs in people with type 1 or type 2 diabetes were included. DATA EXTRACTION Data were charted using a standardized form. Extracted variables included diabetes type, trial design, adaptive features, interventions, end points, and key findings. DATA SYNTHESIS Of 396 articles screened, 6 published adaptive trials met the inclusion criteria: 3 in type 1 diabetes, 1 in type 2 diabetes, and 2 in diabetes-related neuropathy. Most used adaptive features for dose finding, response-adaptive randomization, and sample size reestimation. No published platform, basket, or umbrella trials were identified. Six ongoing adaptive trials in type 1 diabetes were identified through registry searches, four under an adaptive platform master protocol. LIMITATIONS Despite a comprehensive search, some gray literature and unpublished studies may have been missed. Risk of bias was not assessed, consistent with scoping review methodology. CONCLUSIONS Adaptive and master protocol trials remain rare in diabetes. Overcoming barriers through targeted training and awareness, robust regulatory frameworks, and strategic incentives could support broader adoption.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"30 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna R. Kahkoska, Joshua J. Neumiller, Anastasia-Stefania Alexopoulos, Amlan Barik, Elbert S. Huang, Lori M. Laffel, Naushira Pandya, Christine Slyne, Elena Toschi, Ruth S. Weinstock, Medha Munshi
As care for type 1 diabetes (T1D) advances, the number of adults with T1D living into older adulthood (ages ≥65 years) continues to grow. The population of older adults with T1D is highly heterogeneous, and over the life span, various factors may change over time while others may not, necessitating an individualized approach to management. A key care consideration for people with T1D is the ongoing need for exogenous insulin replacement intensive self-monitoring for effective management. At the same time, growing older may bring changes such as increased risk of misdiagnosis of T1D as type 2 diabetes, greater vulnerability to hypoglycemia, accumulating comorbidities and complications, declining independence due to geriatric syndromes, and a growing need for support in using diabetes technologies and navigating complex care transitions. Given the unique clinical and management needs of this population, we sought to present key care challenges in this population and suggest strategies to optimize quality of care in older adults with T1D, including 1) integrating geriatric screenings, age-friendly care frameworks, and regular reassessments into routine T1D management; 2) developing tailored care approaches for cognitive impairment; 3) establishing support systems for diabetes technology use in primary and long-term care settings; and 4) ensuring insurance coverage and access to diabetes technologies and therapies. Forward-thinking strategies to optimize care include individualized glycemic goal setting, the development and adoption of care models that support continuity of diabetes technology use, and individualized management strategies that consider of the goals and capabilities of the person living with T1D and care partners.
{"title":"Challenges and Opportunities for Improving Care for Type 1 Diabetes in Older Adulthood","authors":"Anna R. Kahkoska, Joshua J. Neumiller, Anastasia-Stefania Alexopoulos, Amlan Barik, Elbert S. Huang, Lori M. Laffel, Naushira Pandya, Christine Slyne, Elena Toschi, Ruth S. Weinstock, Medha Munshi","doi":"10.2337/dci25-0078","DOIUrl":"https://doi.org/10.2337/dci25-0078","url":null,"abstract":"As care for type 1 diabetes (T1D) advances, the number of adults with T1D living into older adulthood (ages ≥65 years) continues to grow. The population of older adults with T1D is highly heterogeneous, and over the life span, various factors may change over time while others may not, necessitating an individualized approach to management. A key care consideration for people with T1D is the ongoing need for exogenous insulin replacement intensive self-monitoring for effective management. At the same time, growing older may bring changes such as increased risk of misdiagnosis of T1D as type 2 diabetes, greater vulnerability to hypoglycemia, accumulating comorbidities and complications, declining independence due to geriatric syndromes, and a growing need for support in using diabetes technologies and navigating complex care transitions. Given the unique clinical and management needs of this population, we sought to present key care challenges in this population and suggest strategies to optimize quality of care in older adults with T1D, including 1) integrating geriatric screenings, age-friendly care frameworks, and regular reassessments into routine T1D management; 2) developing tailored care approaches for cognitive impairment; 3) establishing support systems for diabetes technology use in primary and long-term care settings; and 4) ensuring insurance coverage and access to diabetes technologies and therapies. Forward-thinking strategies to optimize care include individualized glycemic goal setting, the development and adoption of care models that support continuity of diabetes technology use, and individualized management strategies that consider of the goals and capabilities of the person living with T1D and care partners.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"161 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVE Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cardiovascular benefits, but whether this is via metabolic improvements or direct effect remains controversial. This study aimed to explore the causal link between GLP-1RAs and myocardial infarction (MI) and quantify the contribution of metabolic improvements. RESEARCH DESIGN AND METHODS Mendelian randomization (MR) was applied to assess the causal relationship between GLP-1RAs and MI, and two-step MR analysis was applied to quantify the mediating role of metabolic traits. The direct effect of GLP-1RAs on MI was evaluated by multivariate Mendelian randomization (MVMR). Genetic variants associated with GLP-1 receptor (GLP-1R) expression (proxying GLP-1RAs) were used as instrumental variables. Genome-wide association studies (GWAS) data for metabolic traits glycated hemoglobin (HbA1c), BMI, lipid profile, and blood pressure were sourced from the Million Veteran Program, serving as mediators. GWAS data for type 2 diabetes mellitus (T2DM) were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, and data for MI were sourced from the UK Biobank/Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease (CARDIoGRAMplusC4D), serving as outcomes. All GWAS data were restricted to European ancestry. RESULTS Higher GLP-1R expression was correlated with a lower risk of T2DM (odds ratio 0.94 [95% CI 0.92, 0.97]) and MI (0.97 [0.95, 1.00]). Metabolic improvements mediated this association: HbA1c (36.67% [3.89, 69.44]), BMI (28.86% [2.62, 55.10]), triglycerides (18.52% [1.47, 35.57]), HDL-cholesterol (18.28% [1.45, 35.12]), and systolic blood pressure (11.55% [0.33, 22.76]). No direct effect of GLP-1R expression on MI was observed after adjusting for metabolic traits (β = −0.003, P = 0.12). CONCLUSIONS GLP-1RAs protect against MI primarily through metabolic improvements, with no direct effect independent of these pathways. These findings support prioritizing metabolic improvements to reduce cardiovascular risk with GLP-1RAs.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）具有心血管益处，但这是通过代谢改善还是直接作用仍存在争议。本研究旨在探讨GLP-1RAs与心肌梗死（MI）之间的因果关系，并量化代谢改善的贡献。研究设计与方法采用孟德尔随机化（Mendelian randomization， MR）评估GLP-1RAs与心肌梗死之间的因果关系，采用两步MR分析量化代谢性状的中介作用。通过多变量孟德尔随机化（MVMR）评估GLP-1RAs对心肌梗死的直接影响。与GLP-1受体（GLP-1R）表达相关的遗传变异（代理GLP-1RAs）被用作工具变量。代谢特征糖化血红蛋白（HbA1c）、BMI、脂质谱和血压的全基因组关联研究（GWAS）数据来自百万退伍军人计划，作为中介。2型糖尿病（T2DM）的GWAS数据来自糖尿病遗传学复制和荟萃分析（图）联盟，心肌梗死的数据来自英国生物银行/冠状动脉疾病基因组广泛复制和荟萃分析加上冠状动脉疾病（CARDIoGRAMplusC4D），作为结局。所有GWAS数据仅限于欧洲血统。结果较高的GLP-1R表达与较低的T2DM（优势比0.94 [95% CI 0.92, 0.97]）和心肌梗死（优势比0.97[0.95,1.00]）风险相关。代谢改善介导了这种关联：HbA1c（36.67%[3.89, 69.44]）、BMI（28.86%[2.62, 55.10]）、甘油三酯（18.52%[1.47,35.57]）、高密度脂蛋白胆固醇（18.28%[1.45,35.12]）和收缩压（11.55%[0.33,22.76]）。调整代谢性状后，GLP-1R表达对心肌梗死无直接影响（β = - 0.003, P = 0.12）。结论：GLP-1RAs主要通过代谢改善来预防心肌梗死，没有独立于这些途径的直接作用。这些发现支持GLP-1RAs优先改善代谢以降低心血管风险。
{"title":"Metabolic Improvement Mediates the Causal Relationship Between GLP-1 Receptor Agonists and Myocardial Infarction: A Mendelian Randomization and Mediation Analysis Study","authors":"Jingkai Tong, Nana Li, Fang Hu, Yingying Yue","doi":"10.2337/dc25-1822","DOIUrl":"https://doi.org/10.2337/dc25-1822","url":null,"abstract":"OBJECTIVE Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cardiovascular benefits, but whether this is via metabolic improvements or direct effect remains controversial. This study aimed to explore the causal link between GLP-1RAs and myocardial infarction (MI) and quantify the contribution of metabolic improvements. RESEARCH DESIGN AND METHODS Mendelian randomization (MR) was applied to assess the causal relationship between GLP-1RAs and MI, and two-step MR analysis was applied to quantify the mediating role of metabolic traits. The direct effect of GLP-1RAs on MI was evaluated by multivariate Mendelian randomization (MVMR). Genetic variants associated with GLP-1 receptor (GLP-1R) expression (proxying GLP-1RAs) were used as instrumental variables. Genome-wide association studies (GWAS) data for metabolic traits glycated hemoglobin (HbA1c), BMI, lipid profile, and blood pressure were sourced from the Million Veteran Program, serving as mediators. GWAS data for type 2 diabetes mellitus (T2DM) were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, and data for MI were sourced from the UK Biobank/Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease (CARDIoGRAMplusC4D), serving as outcomes. All GWAS data were restricted to European ancestry. RESULTS Higher GLP-1R expression was correlated with a lower risk of T2DM (odds ratio 0.94 [95% CI 0.92, 0.97]) and MI (0.97 [0.95, 1.00]). Metabolic improvements mediated this association: HbA1c (36.67% [3.89, 69.44]), BMI (28.86% [2.62, 55.10]), triglycerides (18.52% [1.47, 35.57]), HDL-cholesterol (18.28% [1.45, 35.12]), and systolic blood pressure (11.55% [0.33, 22.76]). No direct effect of GLP-1R expression on MI was observed after adjusting for metabolic traits (β = −0.003, P = 0.12). CONCLUSIONS GLP-1RAs protect against MI primarily through metabolic improvements, with no direct effect independent of these pathways. These findings support prioritizing metabolic improvements to reduce cardiovascular risk with GLP-1RAs.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"30 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An Ran Ran, Jennifer Li Ding, Ziqi Tang, Ching Lam, Truong X. Nguyen, Jiaying Zhou, Shuyi Zhang, Danqi Fang, Dawei Yang, Vincent Ng, Duoru Lin, Haotian Lin, Clement C. Tham, Carmen K.M. Chan, Simon K.H. Szeto, Tien Y. Wong, Sobha Sivaprasad, Carol Y. Cheung
Background Deep learning (DL) has shown promise in delivering diagnostic and economic benefits for detecting diabetic retinopathy (DR) from fundus photographs (FPs). However, evidence synthesis of model validation in prospective, real-world settings remains limited. Purpose To assess the feasibility of implementing DL-DR systems using FPs across different countries by synthesizing prospective validation and economic evidence. Data Sources Five databases were searched until 13 August 2025. Study Selection Studies prospectively assessing diagnostic performance and/or studies conducting economic analyses of DL-DR systems using FPs were selected. Data Extraction Characteristics of all studies, performance parameters of prospective validation studies, and economic outcomes of economic analysis studies were extracted. Data Synthesis Forty-seven studies were included in the meta-analysis. The pooled performance was the highest in detecting vision-threatening DR (area under the receiver operating characteristic curve [AUROC] 0.974), followed by any DR (AUROC 0.965), then referable DR (RDR) (AUROC 0.959). Study region, clinical pathway, mydriasis, image quality control, sample size, grading criteria, reference standard, and model architecture significantly affected model performance in RDR detection. Fifteen studies were included in the economic commentary, showing that DL-based DR screening was cost-effective in high-income countries, whereas results in middle-income countries were mixed, depending on compliance rates, glycemic control, and initial costs. Limitations A paucity of studies assessing multiple severities of DR or diabetic macular edema restricted our ability to perform subgroup analyses. Insights into low-income countries were limited by a lack of studies in these regions. Conclusions DL-DR systems using FPs had high discriminative performance in prospective real-world settings and hold promise to improve cost-effectiveness, especially in high-income countries.
{"title":"Real-World Prospective Validation and Economic Evaluation of Deep Learning-Based Diabetic Retinopathy Detection From Fundus Photographs: A Systematic Review and Meta-analysis","authors":"An Ran Ran, Jennifer Li Ding, Ziqi Tang, Ching Lam, Truong X. Nguyen, Jiaying Zhou, Shuyi Zhang, Danqi Fang, Dawei Yang, Vincent Ng, Duoru Lin, Haotian Lin, Clement C. Tham, Carmen K.M. Chan, Simon K.H. Szeto, Tien Y. Wong, Sobha Sivaprasad, Carol Y. Cheung","doi":"10.2337/dc25-1493","DOIUrl":"https://doi.org/10.2337/dc25-1493","url":null,"abstract":"Background Deep learning (DL) has shown promise in delivering diagnostic and economic benefits for detecting diabetic retinopathy (DR) from fundus photographs (FPs). However, evidence synthesis of model validation in prospective, real-world settings remains limited. Purpose To assess the feasibility of implementing DL-DR systems using FPs across different countries by synthesizing prospective validation and economic evidence. Data Sources Five databases were searched until 13 August 2025. Study Selection Studies prospectively assessing diagnostic performance and/or studies conducting economic analyses of DL-DR systems using FPs were selected. Data Extraction Characteristics of all studies, performance parameters of prospective validation studies, and economic outcomes of economic analysis studies were extracted. Data Synthesis Forty-seven studies were included in the meta-analysis. The pooled performance was the highest in detecting vision-threatening DR (area under the receiver operating characteristic curve [AUROC] 0.974), followed by any DR (AUROC 0.965), then referable DR (RDR) (AUROC 0.959). Study region, clinical pathway, mydriasis, image quality control, sample size, grading criteria, reference standard, and model architecture significantly affected model performance in RDR detection. Fifteen studies were included in the economic commentary, showing that DL-based DR screening was cost-effective in high-income countries, whereas results in middle-income countries were mixed, depending on compliance rates, glycemic control, and initial costs. Limitations A paucity of studies assessing multiple severities of DR or diabetic macular edema restricted our ability to perform subgroup analyses. Insights into low-income countries were limited by a lack of studies in these regions. Conclusions DL-DR systems using FPs had high discriminative performance in prospective real-world settings and hold promise to improve cost-effectiveness, especially in high-income countries.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"29 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edith W. K. Chow, Yingnan Fan, Hongjiang Wu, Eric S. H. Lau, Aimin Yang, Elaine Chow, Alice P. S. Kong, Ronald C. W. Ma, Juliana C. N. Chan, Andrea O. Y. Luk
OBJECTIVE The impact of young-onset hypertension (YOH) on cardiovascular and kidney outcomes in people with type 2 diabetes (T2D) has not been systematically studied. RESEARCH DESIGN AND METHODS This is a retrospective cohort study. We identified individuals with T2D and hypertension who underwent diabetes assessment between 2010 and 2024 in Hong Kong. We defined YOH as hypertension presenting at age <45 years. Individuals with YOH and late-onset hypertension (LOH) were compared with individuals with T2D without hypertension matched for age, sex, diabetes duration, and calendar year. Cox regression was conducted to derive hazard ratios (HRs) and 95% CIs for cardiovascular disease, chronic kidney disease, end-stage kidney disease, and all-cause death in YOH and LOH groups compared with their respective matched control groups. Risk modification by sex was explored in a subgroup analysis. RESULTS A total of 19,224 individuals with YOH and 57,795 individuals with LOH were matched with respective control individuals. YOH was associated with a greater increase in risks for cardiovascular disease (HR 1.83 [95% CI 1.65, 2.03] vs. 1.43 [1.36, 1.5] for LOH), chronic kidney disease (2.58 [2.38, 2.8] vs. 1.81 [1.75, 1.88] for LOH), congestive heart failure (2.58 [1.92, 3.47] vs. 1.81 [1.61, 2.03] for LOH), and death (1.37 [1.22, 1.54] vs. 1.31 [1.25, 1.37] for LOH) (P for interaction < 0.01). Differences in excess risks between YOH and LOH were more pronounced in women than men for cardiovascular disease and coronary heart disease (P for three-way interaction < 0.05). CONCLUSIONS YOH conferred greater risks of cardiovascular and kidney outcomes than LOH in T2D.
目的：年轻发病高血压（YOH）对2型糖尿病（T2D）患者心血管和肾脏预后的影响尚未系统研究。研究设计与方法：回顾性队列研究。我们确定了2010年至2024年间在香港接受糖尿病评估的T2D和高血压患者。我们将YOH定义为出现在年龄&；lt；45年。将YOH合并迟发性高血压（LOH）患者与不伴有高血压的T2D患者进行年龄、性别、糖尿病病程和日历年匹配的比较。进行Cox回归，得出YOH和LOH组与相应对照组相比心血管疾病、慢性肾脏疾病、终末期肾脏疾病和全因死亡的风险比（hr）和95% ci。在亚组分析中探讨了性别对风险的影响。结果YOH患者共19,224例，LOH患者共57,795例。YOH与心血管疾病（LOH的危险度为1.83 [95% CI 1.65, 2.03]比1.43[1.36,1.5]）、慢性肾脏疾病（LOH的危险度为2.58[2.38,2.8]比1.81[1.75,1.88]）、充血性心力衰竭（LOH的危险度为2.58[1.92,3.47]比1.81[1.61,2.03]）和死亡（LOH的危险度为1.37[1.22,1.54]比1.31[1.25,1.37]）相关（P为相互作用& lt； 0.01）。女性患心血管疾病和冠心病的风险在YOH和LOH之间的差异比男性更明显（P为三向相互作用&；lt; 0.05）。结论：与LOH相比，YOH在T2D中具有更大的心血管和肾脏预后风险。
{"title":"Young-Onset Hypertension Confers Higher Risk of Cardiovascular Disease, Kidney Disease, and All-Cause Mortality in Individuals With Type 2 Diabetes: A Propensity Score–Matched Cohort Analysis","authors":"Edith W. K. Chow, Yingnan Fan, Hongjiang Wu, Eric S. H. Lau, Aimin Yang, Elaine Chow, Alice P. S. Kong, Ronald C. W. Ma, Juliana C. N. Chan, Andrea O. Y. Luk","doi":"10.2337/dc25-1839","DOIUrl":"https://doi.org/10.2337/dc25-1839","url":null,"abstract":"OBJECTIVE The impact of young-onset hypertension (YOH) on cardiovascular and kidney outcomes in people with type 2 diabetes (T2D) has not been systematically studied. RESEARCH DESIGN AND METHODS This is a retrospective cohort study. We identified individuals with T2D and hypertension who underwent diabetes assessment between 2010 and 2024 in Hong Kong. We defined YOH as hypertension presenting at age &lt;45 years. Individuals with YOH and late-onset hypertension (LOH) were compared with individuals with T2D without hypertension matched for age, sex, diabetes duration, and calendar year. Cox regression was conducted to derive hazard ratios (HRs) and 95% CIs for cardiovascular disease, chronic kidney disease, end-stage kidney disease, and all-cause death in YOH and LOH groups compared with their respective matched control groups. Risk modification by sex was explored in a subgroup analysis. RESULTS A total of 19,224 individuals with YOH and 57,795 individuals with LOH were matched with respective control individuals. YOH was associated with a greater increase in risks for cardiovascular disease (HR 1.83 [95% CI 1.65, 2.03] vs. 1.43 [1.36, 1.5] for LOH), chronic kidney disease (2.58 [2.38, 2.8] vs. 1.81 [1.75, 1.88] for LOH), congestive heart failure (2.58 [1.92, 3.47] vs. 1.81 [1.61, 2.03] for LOH), and death (1.37 [1.22, 1.54] vs. 1.31 [1.25, 1.37] for LOH) (P for interaction &lt; 0.01). Differences in excess risks between YOH and LOH were more pronounced in women than men for cardiovascular disease and coronary heart disease (P for three-way interaction &lt; 0.05). CONCLUSIONS YOH conferred greater risks of cardiovascular and kidney outcomes than LOH in T2D.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"72 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vera Lehmann, Martin Hilpert, Zohreh Mostaani, Sevada Hovsepyan, Esmé Wallace, Colombine Verzat, Stefan Feuerriegel, Mathias Kraus, James Rosenthal, Gürkan Yilmaz, Mathew Magimai Doss, Christoph Stettler
OBJECTIVE Hypoglycemia is a hazardous diabetes-related emergency. We aimed to develop a machine learning (ML) approach for noninvasive hypoglycemia detection using voice data. RESEARCH DESIGN AND METHODS We collected voice data (540 recordings) with a smartphone in standardized euglycemia and hypoglycemia in two sequential clinical studies in people with type 1 diabetes. Using these data, we trained and evaluated an ML approach to detect hypoglycemia solely based on voice features. RESULTS Twenty-two individuals were included (11 female, age 37.3 ± 12.4 years, HbA1c 7.1 ± 0.5%). The ML approach detected hypoglycemia noninvasively with high accuracy (area under the receiver operating characteristic curve 0.90 ± 0.12 for reading a text aloud and 0.87 ± 0.15 for rapid repetition of syllables [diadochokinetic task]). CONCLUSIONS An ML approach exclusively based on voice data allows for noninvasive hypoglycemia detection, corroborating the potential of ML-based approaches to infer acute health states through voice.
{"title":"Listening to Hypoglycemia: Voice as a Biomarker for Detection of a Medical Emergency Using Machine Learning","authors":"Vera Lehmann, Martin Hilpert, Zohreh Mostaani, Sevada Hovsepyan, Esmé Wallace, Colombine Verzat, Stefan Feuerriegel, Mathias Kraus, James Rosenthal, Gürkan Yilmaz, Mathew Magimai Doss, Christoph Stettler","doi":"10.2337/dc25-1680","DOIUrl":"https://doi.org/10.2337/dc25-1680","url":null,"abstract":"OBJECTIVE Hypoglycemia is a hazardous diabetes-related emergency. We aimed to develop a machine learning (ML) approach for noninvasive hypoglycemia detection using voice data. RESEARCH DESIGN AND METHODS We collected voice data (540 recordings) with a smartphone in standardized euglycemia and hypoglycemia in two sequential clinical studies in people with type 1 diabetes. Using these data, we trained and evaluated an ML approach to detect hypoglycemia solely based on voice features. RESULTS Twenty-two individuals were included (11 female, age 37.3 ± 12.4 years, HbA1c 7.1 ± 0.5%). The ML approach detected hypoglycemia noninvasively with high accuracy (area under the receiver operating characteristic curve 0.90 ± 0.12 for reading a text aloud and 0.87 ± 0.15 for rapid repetition of syllables [diadochokinetic task]). CONCLUSIONS An ML approach exclusively based on voice data allows for noninvasive hypoglycemia detection, corroborating the potential of ML-based approaches to infer acute health states through voice.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"5 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Type 2 diabetes has traditionally been viewed as a chronic, progressive condition. However, recent innovations, such as accessible low-calorie diets and newer weight loss medications, are challenging this paradigm. Evidence from clinical trials and mechanistic studies indicates that intentional weight loss, especially early in the disease course, can meaningfully alter its trajectory through reducing ectopic fat and glycemic levels. New medications that reduce “food noise” are particularly valuable in today’s obesogenic environments, helping patients regain some control over calorie intake and supporting sustainable lifestyle changes. These therapies can lead to weight loss of ≥10% in type 2 diabetes and may enable newly diagnosed individuals to achieve and maintain normoglycemia for many years. Early, substantial weight loss combined with glycemic normalization has the potential to extend life expectancy, reduce or delay complications associated with obesity and hyperglycemia, improve quality of life, and lower long-term care needs. Beyond weight reduction, additional health benefits are offered by these medications, as they also slow atherosclerosis and preserve kidney function. Building on recent American Diabetes Association–European Association for the Study of Diabetes guideline recommendations, we propose that intentional weight loss at or near the time of diagnosis be considered a central strategy in type 2 diabetes management. To support this shift, proof-of-concept trials should be conducted for assessment of the long-term efficacy and durability of this approach. With success, increased competition and broader access to weight loss medications could lower costs and expand availability—even in low- and middle-income countries, where diabetes rates are rising rapidly—supporting a transformative change in the global standard of care.
{"title":"Why Early, Large-scale Weight Loss Is the Future of Type 2 Diabetes Care","authors":"Naveed Sattar, John B. Buse","doi":"10.2337/dci25-0069","DOIUrl":"https://doi.org/10.2337/dci25-0069","url":null,"abstract":"Type 2 diabetes has traditionally been viewed as a chronic, progressive condition. However, recent innovations, such as accessible low-calorie diets and newer weight loss medications, are challenging this paradigm. Evidence from clinical trials and mechanistic studies indicates that intentional weight loss, especially early in the disease course, can meaningfully alter its trajectory through reducing ectopic fat and glycemic levels. New medications that reduce “food noise” are particularly valuable in today’s obesogenic environments, helping patients regain some control over calorie intake and supporting sustainable lifestyle changes. These therapies can lead to weight loss of ≥10% in type 2 diabetes and may enable newly diagnosed individuals to achieve and maintain normoglycemia for many years. Early, substantial weight loss combined with glycemic normalization has the potential to extend life expectancy, reduce or delay complications associated with obesity and hyperglycemia, improve quality of life, and lower long-term care needs. Beyond weight reduction, additional health benefits are offered by these medications, as they also slow atherosclerosis and preserve kidney function. Building on recent American Diabetes Association–European Association for the Study of Diabetes guideline recommendations, we propose that intentional weight loss at or near the time of diagnosis be considered a central strategy in type 2 diabetes management. To support this shift, proof-of-concept trials should be conducted for assessment of the long-term efficacy and durability of this approach. With success, increased competition and broader access to weight loss medications could lower costs and expand availability—even in low- and middle-income countries, where diabetes rates are rising rapidly—supporting a transformative change in the global standard of care.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"144 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peipei Liu, Jiaxi Yang, Dong Hoon Lee, Ling-Jun Li, Wei Wei Pang, Jorge E. Chavarro, Frank B. Hu, Cuilin Zhang
OBJECTIVE We examined the associations of inflammatory and insulinemic diets with type 2 diabetes (T2D) risk among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We followed 4,318 women with a history of GDM in the Nurses’ Health Study II for incident T2D between 1991 and 2019. Empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores were calculated using prevalidated methods. Cox models were used to calculate hazard ratios (HRs) and 95% CIs for the risk of T2D. Additionally, we estimated the least squares means of cardiometabolic biomarkers according to EDIP and EDIH quintiles in a subset of participants who were free of T2D at the time of blood collection. RESULTS During 84,174 person-years of follow-up, 1,037 women developed T2D. After adjusting for major covariates, including BMI, higher EDIP and EDIH scores, which indicated greater dietary inflammatory and insulinemic potential, were associated with an increased risk of T2D. Compared with those for the lowest quintile, adjusted HRs (95% CIs) for the highest quintile were 1.32 (1.06, 1.64) for EDIP and 1.44 (1.14, 1.82) for EDIH (both Ptrend < 0.05). Higher EDIP scores were significantly associated with higher concentrations of insulin and lower levels of HDL cholesterol, and EDIH scores were significantly positively associated with insulin and C-peptide concentrations. CONCLUSIONS Among women with a history of GDM, those with greater dietary inflammatory and insulinemic potential were found to be at a higher risk of T2D and to have unfavorable cardiometabolic profiles.
{"title":"Inflammatory and Insulinemic Dietary Patterns and Risk of Type 2 Diabetes Among Women With a History of Gestational Diabetes Mellitus: A Prospective Study of 84,174 Person-Years of Follow-up","authors":"Peipei Liu, Jiaxi Yang, Dong Hoon Lee, Ling-Jun Li, Wei Wei Pang, Jorge E. Chavarro, Frank B. Hu, Cuilin Zhang","doi":"10.2337/dc25-1919","DOIUrl":"https://doi.org/10.2337/dc25-1919","url":null,"abstract":"OBJECTIVE We examined the associations of inflammatory and insulinemic diets with type 2 diabetes (T2D) risk among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We followed 4,318 women with a history of GDM in the Nurses’ Health Study II for incident T2D between 1991 and 2019. Empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores were calculated using prevalidated methods. Cox models were used to calculate hazard ratios (HRs) and 95% CIs for the risk of T2D. Additionally, we estimated the least squares means of cardiometabolic biomarkers according to EDIP and EDIH quintiles in a subset of participants who were free of T2D at the time of blood collection. RESULTS During 84,174 person-years of follow-up, 1,037 women developed T2D. After adjusting for major covariates, including BMI, higher EDIP and EDIH scores, which indicated greater dietary inflammatory and insulinemic potential, were associated with an increased risk of T2D. Compared with those for the lowest quintile, adjusted HRs (95% CIs) for the highest quintile were 1.32 (1.06, 1.64) for EDIP and 1.44 (1.14, 1.82) for EDIH (both Ptrend &lt; 0.05). Higher EDIP scores were significantly associated with higher concentrations of insulin and lower levels of HDL cholesterol, and EDIH scores were significantly positively associated with insulin and C-peptide concentrations. CONCLUSIONS Among women with a history of GDM, those with greater dietary inflammatory and insulinemic potential were found to be at a higher risk of T2D and to have unfavorable cardiometabolic profiles.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：